학술논문

Single-cell mapping of gene expression landscapes and lineage in the zebrafish embryo
Document Type
article
Source
Science. 360(6392)
Subject
Human Genome
Genetics
1.1 Normal biological development and functioning
Underpinning research
Generic health relevance
Animals
Clonal Evolution
Gene Expression
Gene Expression Regulation
Developmental
Glycoproteins
Intercellular Signaling Peptides and Proteins
Sequence Analysis
RNA
Single-Cell Analysis
Zebrafish
Zebrafish Proteins
General Science & Technology
Language
Abstract
High-throughput mapping of cellular differentiation hierarchies from single-cell data promises to empower systematic interrogations of vertebrate development and disease. Here we applied single-cell RNA sequencing to >92,000 cells from zebrafish embryos during the first day of development. Using a graph-based approach, we mapped a cell-state landscape that describes axis patterning, germ layer formation, and organogenesis. We tested how clonally related cells traverse this landscape by developing a transposon-based barcoding approach (TracerSeq) for reconstructing single-cell lineage histories. Clonally related cells were often restricted by the state landscape, including a case in which two independent lineages converge on similar fates. Cell fates remained restricted to this landscape in embryos lacking the chordin gene. We provide web-based resources for further analysis of the single-cell data.